Methods have been developed in this laboratory to monitor the inflammatory response in human renal transplants during acute rejection episodes, to isolate and analyze the nature and function of allograft-infiltrating cells, and to quantitate antigenicity, immunogenicity and immunosensitivity of graft parenchymal cells. These methods will be applied to expand our knowledge of in situ effector mechanisms in allograft rejection. We will complete the analysis of the inflammatory response in human and rat kidneys, localize the inflammatory cells (T and B blasts, T and B lymphocytes, plasma cells, monocytes and macrophages) in tissue sections and describe their relationship to the different structural organ components (vascular system, glomeruli, proximal and distal tubuli). Expression of constant an allo-specific determinants of HLA (AgB) and DR (Ia) antigens on cellular components of human and rat kidneys, will be defined using specific rabbit antisera to isolated molecules and rat alloantisera. Rat kidney components will be fractionated and tested for their ability to trigger the immune response in vivo. Immunologically specific and nonspecific effector functions of the inflammatory infiltrate (with and without antibody) against various graft cmponents will be analyzed in vitro. We will examine the interactions between specific immune responses and "nonspecific" inflammmation in the rat, and determine which events are essential for rejection and which are compatible with good allograft function. Using fine-needle aspiration cytology, we will continue to monitor the in situ inflammatory response in human renal transplants, explore more specific cytological criteria indicating reversibility/irreversibility of the rejection episode and measure HLA and DR antigenic expression of the surface of parenchymal (endothelial) cells in well-functioning vs. failing transplants. Finally, we plan to perform a clinical trial to minimize the use of glucocorticosteroids in the postoperative immunosuppressive regime, and individualize its administration in counteracting acute rejection episodes.